FAIMS with non-destructive detection of selectively transmitted ions

ABSTRACT

Disclosed is a high field asymmetric waveform ion mobility spectrometer (FAIMS) with optical based detection of selectively transmitted ions. Light from a light source is directed through an optical port in an electrode of the FAIMS. A light detector is provided for receiving light that is one of transmitted and scattered by the selectively transmitted ions within the FAIMS.

[0001] This application claims the benefit of U.S. ProvisionalApplication No. 60/354,711 filed Feb. 8, 2002.

FIELD OF THE INVENTION

[0002] The instant invention relates generally to high field asymmetricwaveform ion mobility spectrometry (FAIMS), more particularly theinstant invention relates to an apparatus and method for non-destructivedetection of ions separated by FAIMS.

BACKGROUND OF THE INVENTION

[0003] High sensitivity and amenability to miniaturization forfield-portable applications have helped to make ion mobilityspectrometry (IMS) an important technique for the detection of manycompounds, including narcotics, explosives, and chemical warfare agentsas described, for example, by G. Eiceman and Z. Karpas in their bookentitled “Ion Mobility Spectrometry” (CRC, Boca Raton, 1994). In IMS,gas-phase ion mobilities are determined using a drift tube with aconstant electric field. Ions are separated in the drift tube on thebasis of differences in their drift velocities. The drift velocity of anion is proportional to the applied electric field strength at lowelectric field strength, for example 200 V/cm, and the mobility, K,which is determined from experimentation, is independent of the appliedelectric field. Additionally, in IMS the ions travel through a bath gasthat is at sufficiently high pressure that the ions rapidly reachconstant velocity when driven by the force of an electric field that isconstant both in time and location. This is to be clearly distinguishedfrom those techniques, most of which are related to mass spectrometry,in which the gas pressure is sufficiently low that, if under theinfluence of a constant electric field, the ions continue to accelerate.

[0004] E. A. Mason and E. W. McDaniel in their book entitled “TransportProperties of Ions in Gases” (Wiley, New York, 1988) teach that at highelectric field strength, for instance fields stronger than approximately5,000 V/cm, the ion drift velocity is no longer directly proportional tothe applied electric field, and K is better represented by K_(h), anon-constant high field mobility term. The dependence of K_(h) on theapplied electric field has been the basis for the development of highfield asymmetric waveform ion mobility spectrometry (FAIMS). Ions areseparated in FAIMS on the basis of a difference in the mobility of anion at high field strength, K_(h), relative to the mobility of the ionat low field strength, K. In other words, the ions are separated due tothe compound dependent behavior of K_(h) as a function of the appliedelectric field strength.

[0005] In general, a device for separating ions according to the FAIMSprinciple has an analyzer region that is defined by a space betweenfirst and second spaced-apart electrodes. Often, the first electrode ismaintained at ground potential while the second electrode has anasymmetric waveform V(t) applied to it. The asymmetric waveform V(t) iscomposed of a repeating pattern including a high voltage component,V_(h), lasting for a short period of time t_(h) and a lower voltagecomponent, V_(l), of opposite polarity, lasting a longer period of timet_(l). The waveform is synthesized such that the integrated voltage-timeproduct, and thus the field-time product, applied to the secondelectrode during each complete cycle of the waveform is zero, forinstance V_(h)t_(h)+V_(l)t_(l)=0; for example +2000 V for 10 μs followedby −1000 V for 20 μs. The peak voltage during the shorter, high voltageportion of the waveform is called the “dispersion voltage” or DV.

[0006] Generally, the ions that are to be separated are entrained in astream of gas flowing through the FAIMS analyzer region, for examplebetween a pair of horizontally oriented, spaced-apart electrodes.Accordingly, the net motion of an ion within the analyzer region is thesum of a horizontal x-axis component due to the stream of gas and atransverse y-axis component due to the applied electric field. Duringthe high voltage portion of the waveform an ion moves with a y-axisvelocity component given by v_(h)=K_(h)E_(h), where E_(h) is the appliedfield, and K_(h) is the high field ion mobility under operating electricfield, pressure and temperature conditions. The distance traveled by theion during the high voltage portion of the waveform is given byd_(h)=v_(h)t_(l)=K_(h)E_(h)t_(h), where t_(h) is the time period of theapplied high voltage. During the longer duration, opposite polarity, lowvoltage portion of the asymmetric waveform, the y-axis velocitycomponent of the ion is v_(l)=KE_(l), where K is the low field ionmobility under ambient pressure and temperature conditions. The distancetraveled is d_(l)=v_(l)t_(l)=KE_(l)t_(l). Since the asymmetric waveformensures that (V_(h)t_(h))+(V_(l)t_(l))=0, the field-time productsE_(h)t_(l), and E_(l)t_(l) are equal in magnitude. Thus, if K_(h) and Kare identical, d_(h) and d_(l) are equal, and the ion is returned to itsoriginal position along the y-axis during the negative cycle of thewaveform. If at E_(h) the mobility K_(h)>K, the ion experiences a netdisplacement from its original position relative to the y-axis. Forexample, if a positive ion travels farther during the positive portionof the waveform, for instance d_(h)>d_(l), then the ion migrates awayfrom the second electrode and eventually will be neutralized at thefirst electrode.

[0007] In order to reverse the transverse drift of the positive ion inthe above example, a constant negative dc voltage called the“compensation voltage” or CV can be applied to the second electrode.This dc voltage prevents the ion from migrating toward either the secondor the first electrode. If ions derived from two compounds responddifferently to the applied high strength electric fields, the ratio ofK_(h), to K may be different for each compound. Consequently, themagnitude of the CV that is necessary to prevent the drift of the iontoward either electrode is also different for each compound. Thus, whena mixture including several species of ions, each with a unique K_(h)/Kratio, is being analyzed by FAIMS, only one species of ion isselectively transmitted to a detector for a given combination of CV andDV. In one type of FAIMS experiment, the applied CV is scanned withtime, for instance the CV is slowly ramped or optionally the CV isstepped from one voltage to a next voltage, and a resulting intensity oftransmitted ions is measured. In this way a CV spectrum showing thetotal ion current as a function of CV, is obtained.

[0008] U.S. Pat. No. 5,420,424, issued to Carnahan and Tarassov on May30, 1995, teaches a FAIMS device having cylindrical electrode geometryand electrometric ion detection, the contents of which are incorporatedherein by reference. The FAIMS analyzer region is defined by an annularspace between inner and outer cylindrical electrodes. In use, ions thatare to be separated are entrained into a flow of a carrier gas and arecarried into the analyzer region via an ion inlet orifice. Once insidethe analyzer region, the ions become distributed all the way around theinner electrode as a result of the carrier gas flow and ion-ionrepulsive forces. The ions are selectively transmitted within theanalyzer region to an ion extraction region at an end of the analyzerregion opposite the ion inlet end. In particular, a plurality of ionoutlet orifices is provided around the circumference of the outerelectrode for extracting the selectively transmitted ions from the ionextraction region for electrometric detection. Of course, theelectrometric detectors provide a signal that is indicative of the totalion current arriving at the detector. Accordingly, the CV spectrum thatis obtained using the Carnahan device does not include informationrelating to an identity of the selectively transmitted ions. It is alimitation of the Carnahan device that the peaks in the CV spectrum arehighly susceptible to being assigned incorrectly. It is anotherlimitation of the Carnahan device that the ions are consumed upon beingdetected at the electrometric detector. Accordingly, it is not possibleto perform further analysis or separation of the ions, or to collect theions for other uses.

[0009] Replacing the electrometric detector with a mass spectrometerdetection system provides an opportunity to obtain additionalexperimental data relating to the identity of ions giving rise to thepeaks in a CV spectrum. For instance, the mass-to-charge (m/z) ratio ofions that are selectively transmitted through the FAIMS at a particularcombination of CV and DV can be measured. Additionally, replacing themass spectrometer with a tandem mass spectrometer makes it possible toperform a full-fledged structural investigation of the selectivelytransmitted ions. Unfortunately, the selectively transmitted ions aredifficult to extract from the analyzer region of the Carnahan device forsubsequent detection by a mass spectrometer. In particular, the orificeplate of a mass spectrometer typically includes a single small samplingorifice for receiving ions for introduction into the mass spectrometer.This restriction is due to the fact that a mass spectrometer operates ata much lower pressure than the FAIMS analyzer. In general, the size ofthe sampling orifice into the mass spectrometer is limited by theefficiency of the mass spectrometer vacuum system. In principle, it ispossible to align the sampling orifice of a mass spectrometer with asingle opening in the FAIMS outer electrode of the Carnahan device;however, such a combination suffers from very low ion transmissionefficiency and therefore poor detection limits. In particular, theCarnahan device does not allow the selectively transmitted ions to beconcentrated for extraction through the single opening. Accordingly,only a small fraction of the selectively transmitted ions are extractedfrom the analyzer region, the vast majority of the selectivelytransmitted ions being neutralized eventually upon impact with anelectrode surface.

[0010] Guevremont et al. describe the use of curved electrode bodies,for instance inner and outer cylindrical electrodes, for producing atwo-dimensional atmospheric pressure ion focusing effect that results inhigher ion transmission efficiencies than can be obtained using, forexample, a FAIMS device having parallel plate electrodes. In particular,with the application of an appropriate combination of DV and CV an ionof interest is focused into a band-like region between the cylindricalelectrodes as a result of the electric fields which change with radialdistance. Focusing the ions of interest has the effect of reducing thenumber of ions of interest that are lost as a result of the ionsuffering a collision with one of the inner and outer electrodes.

[0011] In WO 00/08455, the contents of which are incorporated herein byreference, Guevremont and Purves describe an improved tandem FAIMS/MSdevice, including a domed-FAIMS analyzer. In particular, the domed-FAIMSanalyzer includes a cylindrical inner electrode having a curved surfaceterminus proximate the ion outlet orifice of the FAIMS analyzer region.The curved surface terminus is substantially continuous with thecylindrical shape of the inner electrode and is aligned co-axially withthe ion outlet orifice. During use, the application of an asymmetricwaveform to the inner electrode results in the normal ion-focusingbehavior as described above, and in addition the ion-focusing actionextends around the generally spherically shaped terminus of the innerelectrode. This causes the selectively transmitted ions to be directedgenerally radially inwardly within the region that is proximate theterminus of the inner electrode. Several contradictory forces are actingon the ions in this region near the terminus of the inner electrode. Theforce of the carrier gas flow tends to influence the ions to traveltowards the ion-outlet orifice, which advantageously also prevents theions from migrating in a reverse direction, back towards the ion source.Additionally, the ions that get too close to the inner electrode arepushed back away from the inner electrode, and those near the outerelectrode migrate back towards the inner electrode, due to the focusingaction of the applied electric fields. When all forces acting upon theions are balanced, the ions are effectively captured in every direction,either by forces of the flowing gas, or by the focusing effect of theelectric fields of the FAIMS mechanism. This is an example of athree-dimensional atmospheric pressure ion trap, as described in greaterdetail by Guevremont and Purves in WO 00/08457, the contents of whichare incorporated herein by reference.

[0012] Guevremont and Purves further disclose a near-trapping mode ofoperation for the above-mentioned tandem FAIMS/MS device, which achievesion transmission from the domed-FAIMS to a mass spectrometer with highefficiency. Under near-trapping conditions, the ions that accumulate inthe three-dimensional region of space near the spherical terminus of theinner electrode are caused to leak from this region, being pulled by aflow of gas towards the ion-outlet orifice. The ions that are extractedfrom this region do so as a narrow, approximately collimated beam, whichis pulled by the gas flow through the ion-outlet orifice and into asmaller orifice leading into the vacuum system of the mass spectrometer.Accordingly, such tandem FAIMS/MS devices are highly sensitiveinstruments that are capable of detecting and identifying ions ofinterest at part-per-billion levels.

[0013] Unfortunately, the tandem FAIMS/MS arrangement suffers from anumber of limitations. In particular, ions that are analyzed by massspectrometry cannot be collected or analyzed further. Instead, the ionsare neutralized upon impact with a detector element of the massspectrometer, such as for instance an electron multiplier. Accordingly,it is not possible to analyze ions that are selectively transmitted by afirst FAIMS device before they are provided to a second FAIMS device foradditional separation in a tandem FAIMS/FAIMS arrangement. Similarly, itis not possible to provide the mass analyzed ions to a second detectorfor subsequent analysis by a complementary technique. Of course,analysis by a complementary technique provides an opportunity to probecharacteristics of the ions other than mass-to-charge (m/z) ratio. Forexample, using an infrared analyzer to obtain the infrared spectrum ofthe ions provides information relating to the presence of specificchemical functional groups, etc.

[0014] Furthermore, the size of the sampling orifice into the massspectrometer is very small, being limited by the efficiency of the massspectrometer vacuum system. In order to transmit as many ions aspossible from the FAIMS analyzer to the mass spectrometer, it isnecessary to dispose the sampling orifice immediately adjacent to theion-outlet orifice, such that widening of the ion beam as a result ofion diffusion and ion-ion repulsion is minimized. As will be obvious toone of skill in the art, the insertion of a non-destructive analyzer,such as for instance the above-mentioned infrared analyzer, intermediatethe sampling orifice and the ion-outlet orifice results in a longer ionpath to the mass spectrometer, which increases the amount of time forthe ion beam to spread out radially. Of course, the efficiency ofintroducing ions into the mass spectrometer decreases as the crosssection of the ion beam increases, and dilute samples may produceinsufficient signal intensity for obtaining meaningful results.

[0015] It would be advantageous to provide a FAIMS apparatus including adetection system that overcomes the limitations of the prior art.

SUMMARY OF THE INVENTION

[0016] In accordance with an aspect of the invention there is providedan apparatus for separating ions in the gas phase, comprising: a highfield asymmetric waveform ion mobility spectrometer comprising twoelectrodes defining an analyzer region therebetween, the two electrodesdisposed in a spaced apart arrangement for allowing ions to propagatetherebetween and for providing an electric field within the analyzerregion resulting from the application of an asymmetric waveform voltageto at least one of the two electrodes and from the application of acompensation voltage to at least one of the two electrodes, forselectively transmitting a first type of ion along an average ion flowpath within the analyzer region at a given combination of asymmetricwaveform voltage and compensation voltage; and, an optical port disposedadjacent to a portion of the analyzer region other than a portionincluding an origin of the average ion flow path, the optical portformed of a light transmissive material other than a gas, which materialis transmissive to light within a predetermined range of wavelengths forsupporting the propagation of light having a wavelength within thepredetermined range of wavelengths between the analyzer region and aregion that is external to the analyzer region.

[0017] In accordance with another aspect of the invention there isprovided an apparatus for separating ions in the gas phase, comprising:a high field asymmetric waveform ion mobility spectrometer comprisingtwo electrodes defining an analyzer region therebetween, the twoelectrodes disposed in a spaced apart arrangement for allowing a gasflow to pass therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting a first type of ion along an average ion flowpath within the analyzer region between an origin of the ion flow pathand an ion outlet orifice of the analyzer region at a given combinationof asymmetric waveform voltage and compensation voltage, whereby, inuse, at least one of the asymmetric waveform voltage, the compensationvoltage and the gas flow are adjustable, so as to confine some of theselectively transmitted ions within a 3-dimensional region of spacewithin the analyzer region and adjacent to the ion outlet orifice; and,a first optical port disposed within a surface of one of the twoelectrodes and adjacent to the analyzer region at a point that isgenerally aligned with the 3-dimensional region of space within theanalyzer region and adjacent to the ion outlet orifice, the firstoptical port formed of a material other than a gas, which material istransmissive to light within a predetermined range of wavelengths forpropagating light including information relating to the selectivelytransmitted ions therethrough.

[0018] In accordance with still another aspect of the invention there isprovided an apparatus for separating ions in the gas phase, comprising:a high field asymmetric waveform ion mobility spectrometer comprisingtwo electrodes defining an analyzer region therebetween, the twoelectrodes disposed in a spaced apart arrangement for allowing a gasflow to pass therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting a first ion type in the analyzer region at agiven combination of asymmetric waveform voltage and compensationvoltage, whereby, in use, at least one of the asymmetric waveformvoltage, the compensation voltage and the gas flow are adjustable, so asto confine some of the selectively transmitted ions within a3-dimensional region of space within the analyzer region; a firstoptical port disposed within a surface of one of the two electrodes andadjacent to a portion of the analyzer region including the 3-dimensionalregion of space, the first optical port for propagating incident lightalong an optical path including the first optical port and the3-dimensional region of space; and, a second optical port disposedwithin a surface of one of the two electrodes and adjacent to theportion of the analyzer region including the 3-dimensional region ofspace, the second optical port for propagating other light, resultingfrom the passage of the incident light through the 3-dimensional regionof space, therethrough.

[0019] In accordance with yet another aspect of the invention there isprovided an apparatus for separating ions in the gas phase, comprising:a high field asymmetric waveform ion mobility spectrometer comprisingtwo electrodes defining an analyzer region therebetween, the twoelectrodes disposed in a spaced apart arrangement for allowing ions topropagate therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting a first ion type in the analyzer region at agiven combination of asymmetric waveform voltage and compensationvoltage; and, a probe signal generator for generating a probe signalwhich when applied to the selectively transmitted ions results in lightincluding information relating to the selectively transmitted ionswithin the analyzer region.

[0020] In accordance with yet another aspect of the invention there isprovided an apparatus for separating ions in the gas phase, comprising:a high field asymmetric waveform ion mobility spectrometer comprisingtwo electrodes defining an analyzer region therebetween, the twoelectrodes disposed in a spaced apart arrangement for allowing a gasflow to pass therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting a first ion type in the analyzer region at agiven combination of asymmetric waveform voltage and compensationvoltage, whereby, in use, the asymmetric waveform voltage, thecompensation voltage and the gas flow are adjustable, so as to confinesome of the selectively transmitted ions within a 3-dimensional regionof space within the analyzer region; a first optical port disposedwithin a surface of one of the two electrodes and adjacent to a portionof the analyzer region including the 3-dimensional region of space; and,a light source disposed external to the analyzer region and in opticalcommunication with the first optical port for providing incident lighthaving a wavelength within a predetermined range of wavelengths to theselectively transmitted ions within the 3-dimensional region of space.

[0021] In accordance with yet another aspect of the invention there isprovided a method for separating ions in the gas phase, comprising thesteps of: separating a mixture of ions including ions of a first type byselectively transmitting the ions of the first type through an analyzerregion of a high field asymmetric waveform ion mobility spectrometeralong an ion flow path between an ion inlet end of the analyzer regionand an ion outlet end of the analyzer region; providing a stimulus tothe selectively transmitted ions within at least a portion of theanalyzer region for producing light including information relating tothe selectively transmitted ions; and providing the light includinginformation relating to the selectively transmitted ions to a lightdetector that is external to the analyzer region.

[0022] In accordance with yet another aspect of the invention there isprovided a method for separating ions in the gas phase, comprising thesteps of: separating a mixture of ions including ions of a first type byselectively transmitting the ions of a first type through an analyzerregion of a high field asymmetric waveform ion mobility spectrometeralong an ion flow path between an ion inlet of the analyzer region andan ion outlet of the analyzer region; confining some of the selectivelytransmitted ions within a 3-dimensional region of space adjacent to theion outlet and within the analyzer region; directing incident lightthrough the 3-dimensional region of space adjacent to the ion outlet andwithin the analyzer region for interacting with the selectivelytransmitted ions within the 3-dimensional region of space adjacent tothe ion outlet and within the analyzer region; and, detecting lightincluding information relating to the selectively transmitted ionsresulting from an interaction between the incident light and theselectively transmitted ions confined within the 3-dimensional region ofspace adjacent to the ion outlet and within the analyzer region.

[0023] In accordance with yet another aspect of the invention there isprovided a method for separating ions in the gas phase, comprising thesteps of: effecting a first separation of the ions within a portion ofan analyzer region between an ion inlet end of the analyzer region and areaction portion of the analyzer region; affecting the ions within thereaction portion of the analyzer region so as to induce a structuralchange of the ions; and, effecting a second separation of the ionswithin a portion of an analyzer region between the reaction portion ofthe analyzer region and an ion outlet end of the analyzer region.

[0024] In accordance with yet another aspect of the invention there isprovided an apparatus for separating ions in the gas phase, comprising:a high field asymmetric waveform ion mobility spectrometer comprisingtwo electrodes defining an analyzer region therebetween, the twoelectrodes disposed in a spaced apart arrangement for allowing ions topropagate therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting a first type of ion along an average ion flowpath within the analyzer region at a given combination of asymmetricwaveform voltage and compensation voltage; an optical port disposedwithin a surface of one of the two electrodes and adjacent to an iondetecting portion of the analyzer region, the optical port forpropagating light including information relating to the selectivelytransmitted ions therethrough; and, a light detector disposed externalto the ion detecting portion of the analyzer region and in opticalcommunication with the optical port for receiving the light includinginformation relating to the selectively transmitted ions within the iondetecting portion and for providing an electrical signal relating to atleast an intensity of the received light.

[0025] In accordance with yet another aspect of the invention there isprovided an apparatus for separating ions in the gas phase, comprising:a high field asymmetric waveform ion mobility spectrometer comprisingtwo electrodes defining an analyzer region therebetween, the twoelectrodes disposed in a spaced apart arrangement for allowing ions topropagate therebetween and for providing an electric field within theanalyzer region resulting from the application of an asymmetric waveformvoltage to at least one of the two electrodes and from the applicationof a compensation voltage to at least one of the two electrodes, forselectively transmitting a first type of ion along an average ion flowpath within the analyzer region at a given combination of asymmetricwaveform voltage and compensation voltage; and, an optical detectorspaced apart from the average ion flow path for receiving lightincluding information relating to the selectively transmitted ionswithin the average ion flow path so as to support a nondestructivedetermination of a characteristic of the selectively transmitted ions.

[0026] In accordance with yet another aspect of the invention there isprovided a method for separating ions in the gas phase, comprising thesteps of: separating a mixture of ions including ions of a first type byselectively transmitting the ions of the first type through an analyzerregion of a high field asymmetric waveform ion mobility spectrometeralong an average ion flow path between an ion inlet end of the analyzerregion and an ion outlet end of the analyzer region; detecting lightincluding information relating to the selectively transmitted ions usinga light detector that is spaced apart from the average ion flow path;and, determining a characteristic of the selectively transmitted ionsbased on the detected light including information relating to theselectively transmitted ions.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Exemplary embodiments of the invention will now be described inconjunction with the following drawings, in which similar referencenumbers designate similar items:

[0028]FIG. 1 is a simplified cross-sectional view of a tandem FAIMS/MSapparatus;

[0029]FIG. 2a is a side cross-sectional view of a FAIMS device accordingto a first embodiment of the instant invention;

[0030]FIG. 2b is a simplified end-on view of the FAIMS device of FIG.2a;

[0031]FIG. 2c is an enlarged view of a first optical port configurationfor use with the FAIMS device of FIG. 2a;

[0032]FIG. 2d is an enlarged view of a second optical port configurationfor use with the FAIMS device of FIG. 2a;

[0033]FIG. 2e is an enlarged view of a third optical port configurationfor use with the FAIMS device of FIG. 2a;

[0034]FIG. 2f is an enlarged view of a fourth optical port configurationfor use with the FAIMS device of FIG. 2a;

[0035]FIG. 3a is a side cross-sectional view of another FAIMS deviceaccording to the first embodiment of the instant invention;

[0036]FIG. 3b is a simplified end-on view of the FAIMS device of FIG.3a;

[0037]FIG. 4 is a side cross-sectional view of the FAIMS deviceaccording to the first embodiment of the instant invention coupled to amass spectrometer;

[0038]FIG. 5 is a side cross-sectional view of the FAIMS deviceaccording to the first embodiment of the instant invention coupled to asecond FAIMS device and a mass spectrometer;

[0039]FIG. 6a is a side cross-sectional view of a FAIMS device accordingto a second embodiment of the instant invention;

[0040]FIG. 6b is a simplified end-on view of the FAIMS device of FIG.5a;

[0041]FIG. 7a is a side cross-sectional view of another FAIMS deviceaccording to the second embodiment of the instant invention;

[0042]FIG. 7b is a simplified end-on view of the FAIMS device of FIG.6a;

[0043]FIG. 8 is a side cross-sectional view of a FAIMS device accordingto a third embodiment of the instant invention;

[0044]FIG. 9 is a side cross-sectional view of another FAIMS deviceaccording to embodiment of the instant invention;

[0045]FIG. 10 is a simplified flow diagram for a method of detectingselectively transmitted ions according to the first embodiment of theinstant invention;

[0046]FIG. 11 is a simplified flow diagram for a method of detectingselectively transmitted ions according to the second embodiment of theinstant invention;

[0047]FIG. 12 is a simplified flow diagram for a method of affecting theselectively transmitted ions; and,

[0048]FIG. 13 is a simplified flow diagram for a method of affecting theselectively transmitted ions.

DETAILED DESCRIPTION OF THE DRAWINGS

[0049] The following description is presented to enable a person skilledin the art to make and use the invention, and is provided in the contextof a particular application and its requirements. Various modificationsto the disclosed embodiments will be readily apparent to those skilledin the art, and the general principles defined herein may be applied toother embodiments and applications without departing from the spirit andthe scope of the invention. Thus, the present invention is not intendedto be limited to the embodiments disclosed, but is to be accorded thewidest scope consistent with the principles and features disclosedherein. Throughout the disclosure and in the claims that follow, theterm “light including information relating to the selectivelytransmitted ions” is defined as one of scattered light, emitted lightand transmitted incident light having a wavelength within one of theinfrared, ultraviolet and visible regions of the electromagneticspectrum, wherein one of the intensity, frequency, polarization andperiodicity of intensity variation of the light is indicative of, forexample, one of an ionic chemical structure, an ionic conformationalstate, an ionic density and a relative ionic density of the selectivelytransmitted ions within a FAIMS analyzer region. In addition, the term“average ion flow path” is defined as the net trajectory of the ions asa result of one of a carrier gas flow through the analyzer region and anelectrical field gradient within the analyzer region, although theindividual ions also experience an oscillatory motion between theelectrodes as a result of the applied asymmetric waveform voltage.

[0050] Referring to FIG. 1, shown is a simplified cross-sectional viewof a tandem FAIMS/MS apparatus. In particular, a domed-FAIMS device 2having cylindrical electrode geometry is shown in fluid communicationwith a mass spectrometer 28. The domed-FAIMS device 2 includes inner andouter cylindrical electrodes 4 and 16, respectively, which are supportedby an electrically insulating material 10 in an overlapping,spaced-apart arrangement. The generally annular space between the innerelectrode 4 and the outer electrode 16 defines a FAIMS analyzer region12. The width of the analyzer region is approximately uniform around thecircumference of the inner electrode 4, and extends around a curvedsurface terminus 5 of the inner electrode 4. An ion inlet orifice 111 isprovided through the outer electrode 16 for introducing ions from an ionsource 26 into the analyzer region 12. A flow of a carrier gas, which isrepresented in the figure by a series of closed-headed arrows, isprovided within the analyzer region 12 to carry the ions toward an ionoutlet orifice 14 located opposite the curved surface terminus 5 of theinner electrode 4. An orifice 19 within a curtain plate electrode 17allows for the flow of a portion of the carrier gas in a direction thatis counter-current to the direction in which the ions are traveling nearthe ion inlet 11, so as to desolvate the ions before they are introducedinto the analyzer region 12. The inner electrode 4 is provided with anelectrical contact 8 through the insulating material 10 for connectionto a power supply 6 that during use is capable of applying a highvoltage asymmetric waveform voltage (DV) and a low voltage dccompensation voltage (CV) to the inner FAIMS electrode 4.

[0051] The mass spectrometer 28 is disposed external to the FAIMSanalyzer region 12, and includes an orifice plate 22 having an inletorifice 20 extending therethrough. As will be apparent to one of skillin the art, the size of the inlet orifice 20 is typically very small,being limited by the efficiency of the mass spectrometer vacuum system.The inlet orifice 20 in the orifice plate 22 is aligned with the ionoutlet orifice 14 of the domed-FAIMS device 2 such that ions beingextracted through the ion outlet orifice 14 enter the mass spectrometerinlet orifice 20. Those ions that pass through the orifice 20 in theorifice plate 22 travel to a skimmer cone 24 within the differentiallypumped region of the mass spectrometer 28, and are analyzed within amass analyzer 18 on the basis of their mass-to-charge ratio. The massspectrometer includes a not illustrated detector, such as for instancean electron multiplier, for providing an electrical signal that isproportional to a detected ion current.

[0052] During use, ions are produced at the ion source 26 from asuitable sample containing a species of interest. Typically, a mixtureincluding a plurality of different ion types is produced when the sampleis ionized. A potential gradient is used in order to accelerate the ionsof the mixture away from the ion source 26, through the orifice 19 inthe curtain plate electrode 17, and toward the ion inlet orifice 11,where the ions become entrained in the carrier gas flow and are carriedinto the FAIMS analyzer region 12. Once inside the FAIMS analyzer region12, the ions are carried through an electric field that is formed withinthe FAIMS analyzer region 12 by the application of the DV and the CV tothe inner FAIMS electrode 4 via the electrical contact 8. Ion separationoccurs within the FAIMS analyzer region 12 on the basis of the highfield mobility properties of the ions. Those ions of the mixture thathave a stable trajectory for a particular combination of DV and CV areselectively transmitted through the FAIMS analyzer region 12, whilstother ions of the mixture collide with an electrode surface and arelost. Since the electric field also extends around the curved surfaceterminus 5, the selectively transmitted ions tend to be directedgenerally radially inwardly towards the ion outlet orifice 14. Neartrapping conditions are created within the analyzer region 12 byadjusting at least one of the carrier gas flow rate, the carrier gascomposition, the applied CV, the applied DV, the distance between thecurved surface terminus 5 and the ion outlet orifice 14, the potentialthat is applied to the orifice plate 22, the temperature of the carriergas and the pressure of the carrier gas. Under trapping conditions,which are created within the analyzer region 12 by adjusting at leastone of the above-mentioned parameters to a different value, theselectively transmitted ions accumulate within a 3-dimensional region ofspace proximate the curved surface terminus 5. Under near-trappingconditions the ions also accumulate within the 3-dimensional region ofspace proximate the curved surface terminus 5, except that a lower iondensity is achieved when operating under near-trapping conditions, sincethe ions are being continually extracted from the 3-dimensional regionof space as an approximately collimated beam of ions. The extracted ionsare carried by the carrier gas flow through the ion outlet orifice 14.

[0053] Referring now to FIG. 2a, shown is a side cross-sectional view ofa FAIMS device 30 according to a first embodiment of the instantinvention. The FAIMS device 30, in the form of a domed-FAIMS device,includes inner and outer cylindrical electrodes 32 and 44, respectively,which are supported by an electrically insulating material 38 in anoverlapping, spaced-apart arrangement. The generally annular spacebetween the inner electrode 32 and the outer electrode 44 defines aFAIMS analyzer region 40. The width of the analyzer region isapproximately uniform around the circumference of the inner electrode32, and extends around a curved surface terminus 33 of the innerelectrode 32. An ion inlet orifice 35 is provided through the outerelectrode 44 for introducing ions from an ion source 54 into theanalyzer region 40. A flow of a carrier gas, which is represented in thefigure by a series of closed-headed arrows, is provided within theanalyzer region 40 to carry the ions toward an ion outlet orifice 42located opposite the curved surface terminus 33 of the inner electrode32. An orifice 39 within a curtain plate electrode 37 allows for theflow of a portion of the carrier gas in a direction that iscounter-current to the direction in which the ions are traveling nearthe ion inlet 35, so as to desolvate the ions before they are introducedinto the analyzer region 40. The inner electrode 32 is provided with anelectrical contact 36 through the insulating material 38 for connectionto a power supply 34 that during use is capable of applying a highvoltage asymmetric waveform voltage (DV) and a low voltage dccompensation voltage (CV) to the inner FAIMS electrode 32.

[0054] During use, ions are produced at the ion source 54 from asuitable sample containing a species of interest. Typically, a mixtureincluding a plurality of different ion types is produced when the sampleis ionized. A potential gradient is used in order to accelerate the ionsof the mixture away from the ion source 54, through the orifice 39 inthe curtain plate electrode 37, and toward the ion inlet orifice 35,where the ions become entrained in the carrier gas flow and are carriedinto the FAIMS analyzer region 40. Once inside the FAIMS analyzer region40, the ions are carried through an electric field that is formed withinthe FAIMS analyzer region 40 by the application of the DV and the CV tothe inner FAIMS electrode 32 via the electrical contact 36. Ionseparation occurs within the FAIMS analyzer region 40 on the basis ofthe high field mobility properties of the ions. Those ions of themixture that have a stable trajectory for a particular combination of DVand CV are selectively transmitted through the FAIMS analyzer region 40,whilst other ions of the mixture collide with an electrode surface andare lost. Since the electric field also extends around the curvedsurface terminus 33, the selectively transmitted ions tend to bedirected generally radially inwardly towards the ion outlet orifice 42.Near trapping conditions are created within the analyzer region 40 byadjusting at least one of the carrier gas flow rate, the carrier gascomposition, the applied CV, the applied DV, the distance between thecurved surface terminus 33 and the ion outlet orifice 42, thetemperature of the carrier gas and the pressure of the carrier gas.Under trapping conditions, which are created within the analyzer region40 by adjusting at least one of the above-mentioned parameters to adifferent value, the selectively transmitted ions accumulate within a3-dimensional region of space proximate the curved surface terminus 33.Under near-trapping conditions the ions also accumulate within the3-dimensional region of space proximate the curved surface terminus 33,except that a lower ion density is achieved when operating undernear-trapping conditions, since the ions are being continually extractedfrom the 3-dimensional region of space as an approximately collimatedbeam of ions. The extracted ions are carried by the carrier gas flowthrough the ion outlet orifice 42.

[0055] Referring still to FIG. 2a, an infrared light source 50 isprovided for launching infrared light, shown schematically with a dashedline ending with an open-headed arrow, through a first optical port 48in the outer FAIMS electrode 44. For example, the infrared light source50 produces infrared light and directs a beam of the produced infraredlight along an optical path including the first optical port 48.Preferably, the first optical port 48 is disposed along the length ofthe outer electrode 44 at a point that is substantially aligned with the3-dimensional region of space proximate the spherical terminus 33.Accordingly, the infrared light from infrared light source 50 isdirected through a region of higher ion density of the selectivelytransmitted ions within the 3-dimensional region of space. A secondoptical port 49 is disposed within the outer FAIMS electrode 44 at apoint that is approximately opposite the first optical port 48, forreceiving the infrared light after it has passed through the3-dimensional region of space proximate the spherical terminus 33. Alight detector 52 is provided in optical communication with the secondoptical port 49 for receiving infrared light propagating therethrough,and for providing an electrical signal relating to an intensity of thereceived infrared light. Of course, the first optical port 48 and thesecond optical port 49 are preferably of a size that is sufficientlylarge to support the propagation of the infrared light therethrough.Furthermore, the first optical port 48 and the second optical port 49are preferably of a size that is sufficiently small such that theelectric fields within the analyzer region are substantially unaffectedby the discontinuity in the electrode material.

[0056] During use, trapping conditions are preferably maintained withinthe analyzer region as described above, such that the selectivelytransmitted ions accumulate within the 3-dimensional region of spaceadjacent to the spherical terminus 33 of the inner electrode 32. Thisregion of space becomes enriched with ions relative to other regions ofspace within the analyzer region. The infrared light beam is passedthrough the 3-dimensional region of space, where the accumulated ionsmay absorb some of the infrared light. The absorption of infrared lightis detected at the light detector 52. Preferably, the absorption ismeasured as a function of frequency of the infrared light. By scanningthe frequency of the infrared light, a fingerprint spectrum is obtainedthat is specific for a given compound. A common method for determiningthe identity of an unknown compound using solid samples involvescomparing the unknown sample with a library of known compounds andreporting the most likely matches. A similar library can be envisionedusing gas-phase ions. In this way, the infrared light beam is used toprobe ions within the FAIMS analyzer region 40. Accordingly, theinfrared light source 50 is an example of a probe signal generator. Ofcourse, light having a wavelength selected from other regions of theelectromagnetic spectrum may also be used to probe the ions, such as forexample ultraviolet light and visible light. Furthermore, in addition tosimply measuring the amount of light that is absorbed by the ions,probing of the ions may include any interaction between an incidentlight beam and the ions that results in a change to either the ions orthe light beam. For example, probing may result in a conformationalchange to the ions, a dissociation of neutral or charged species fromcluster ions, a change of the vibrational state of the ions etc. Furtherstill, probing may result in one of absorption of a portion of theincident light beam, scattering of a portion of the incident light beam,fluorescence by the ions, and emission of light by one of the ions andthe gas molecules in the vicinity of the ions.

[0057] Optionally, the analyzer is operated in the near-trapping mode soas to continually extract ions from the 3-dimensional region of space.For example, the extracted ions are provided to one of a second FAIMSdevice and a mass spectrometer for additional separation and detection.Further optionally, the analyzer is operated in a pulsed trapping modeso as to provide packets of ions at intervals of time for one ofadditional separation and detection.

[0058] Referring now to FIG. 2b, shown is a simplified end-on view ofthe FAIMS device of FIG. 2a. Elements labeled with the same numeralshave the same function as those illustrated in FIG. 2a. In particular,the infrared light source 50 and the light detector 52 are arranged onerelative to the other and relative to the FAIMS outer electrode 44 suchthat the infrared light travels between the source 50 and the detector52 through the 3-dimensional region of space proximate the sphericalterminus 33. As such, the infrared radiation is used to probe an area ofhigher ion density within the FAIMS analyzer region 40. It is anadvantage of the apparatus according to the first embodiment of theinstant invention that the infrared light that is used to probe theaccumulated ions does not result in the ions being consumed orstructurally changed. Accordingly, ions that are detected can besubsequently analyzed or otherwise manipulated using complimentaryanalysis methods or complimentary separation techniques, respectively.Furthermore, the ability to increase the concentration of ions in thegas phase, thereby overcoming the natural tendency of the like-chargedions to repel one-another, makes it possible to perform opticaldetection of samples that otherwise would be far too dilute to providemeaningful results.

[0059] Referring now to FIG. 2c, shown is an enlarged simplified view ofa first optical port configuration for use with the FAIMS deviceaccording to the first embodiment of the instant invention. A lighttransmissive window 51 c is disposed within the outer electrode 44. Thelight transmissive window 51 c is constructed of a material, other thana gas, that is substantially transmissive to light within a wavelengthrange of interest. For example, the light transmissive window 51 c isconstructed of a material that is substantially transmissive to lightwithin the infrared region of the electromagnetic spectrum. Suitablematerials for constructing the light transmissive window 51 c will bereadily apparent to one of skill in the art. Some non-limiting examplesof suitable window materials include; sodium chloride (NaCl), potassiumbromide (KBr) and calcium chloride (CaCl₂). Preferably, the firstoptical port 48 and the second optical port 49 each include a lighttransmissive window 51 c that is constructed using similar materials.Preferably, the light transmissive window 51 c forms a gas tight sealwith the outer electrode 44. Preferably, the light transmissive window51 c includes a first outer surface that is approximately continuouswith an inner surface of the outer electrode 44, and a second outersurface that is approximately continuous with an outer surface of theouter electrode 44.

[0060] Referring now to FIG. 2d, shown is an enlarged simplified view ofa second optical port configuration for use with the FAIMS deviceaccording to the first embodiment of the instant invention. A lighttransmissive window 51 d is disposed within the outer electrode 44. Thelight transmissive window 51 d is constructed of a material, other thana gas, that is substantially transmissive to light within a wavelengthrange of interest. For example, the light transmissive window 51 d isconstructed of a material that is substantially transmissive to lightwithin the infrared region of the electromagnetic spectrum. Preferably,the first optical port 48 and the second optical port 49 each include alight transmissive window 51 d that is constructed using similarmaterials. Preferably, the light transmissive window 51 d forms a gastight seal with the outer electrode 44. Preferably, the lighttransmissive window 51 d includes a first outer surface recessed withinan opening through the outer electrode 44. Since the light transmissivewindow 51 d is generally constructed from an insulating material, ionscolliding therewith cause a charge buildup that affects the electricfield within the analyzer region due to the applied DV and the appliedCV. The effect of such a charge buildup is expected to diminish when thewindow material is recessed relative to the inner surface of the outerelectrode 44.

[0061] Referring now to FIG. 2e, shown is an enlarged simplified view ofa third optical port configuration for use with the FAIMS deviceaccording to the first embodiment of the instant invention. An opticallytransmissive portion 51 e of, for example, the light detector 52 isdisposed immediately adjacent to the outer surface of the outerelectrode 44. Preferably, the optically transmissive portion 51 e formsa gas-tight seal against the outer surface of the outer electrode 44.Optionally, the optically transmissive portion 51 e is a lighttransmissive window separate from the light detector 52, which lighttransmissive window preferably forms a gas-tight seal against the outersurface of the outer electrode 44.

[0062] Referring now to FIG. 2f, shown is an enlarged simplified view ofa fourth optical port configuration for use with the FAIMS deviceaccording to the first embodiment of the instant invention. The fourthoptical port configuration does not include a non-gaseous materialdisposed within an opening through the outer electrode 44. For example,the fourth optical port configuration includes an opening through theouter electrode 44 which allows light to propagate therethrough andwhich also allows gas and/or ions to escape from the analyzer region 40.Optionally, the fourth optical port configuration includes a source of asupplemental gas flow, as is shown in FIG. 2f, for directing asupplemental gas flow into the analyzer region via the opening throughthe outer electrode 44, in order to prevent the gas and/or ions fromescaping from the analyzer region 40.

[0063] Referring now to FIG. 3a, shown is a side cross-sectional view ofanother FAIMS device 61 according to a first embodiment of the instantinvention. Elements labeled with the same numerals have the samefunction as those illustrated in FIG. 2a. The FAIMS device 61 includesan outer electrode 53 in the form of a tube having an approximatelyuniform cross-section taken at any point along a longitudinal axisthereof. First and second optical ports 55 and 57, respectively, areprovided in the outer electrode 53 for supporting the propagation oflight therethrough. The outer electrode 53 does not maintain anapproximately constant spacing to the inner electrode 32 about thecurved surface terminus 33. Accordingly, an electrically isolated plate,referred to as the trapping plate 59, is disposed adjacent to the outerelectrode 53. The trapping plate 59 is used to manipulate the fields inthe trapping region adjacent to the spherical terminus 33 of the innerelectrode 32. An ion outlet orifice 63 in the trapping plate 59 isprovided for extracting ions from the analyzer region 46. The ion outletorifice 63 in the trapping plate 59 performs substantially the samefunction as the ion outlet orifice 42 in the outer FAIMS electrode 44 ofFIG. 2a. Near-trapping conditions are created within a 3-dimensionalregion of space within the FAIMS analyzer region 46 and adjacent to thecurved surface terminus 33, by adjusting at least one of the carrier gasflow rate, the carrier gas composition, the applied CV, the applied DV,the distance between the curved surface terminus 33 and the ion outletorifice 63, the temperature of the carrier gas, the pressure of thecarrier gas and the potential that is applied to the trapping plate 59.

[0064] Referring now to FIG. 3b, shown is a simplified end-on view ofthe FAIMS device of FIG. 3a. Elements labeled with the same numeralshave the same function as those illustrated in FIG. 3a. In particular,the infrared source 50 and the detector 52 are arranged relative to eachother and relative to the outer electrode 53 such that infrared lightfrom the source 50 travels through the first optical port 55, passesthrough the 3-dimensional region of space proximate the curved surfaceterminus 33, and to a first mirror surface 67. The light is redirectedby the first mirror surface 67, to pass through the 3-dimensional regionof space proximate the curved surface terminus 33 a second time, and toarrive at a second mirror surface 65. Similarly, the second mirrorsurface redirects the light a second time, to pass through the3-dimensional region of space proximate the curved surface terminus 33 athird time, after which the light propagates through the second opticalport 57, finally arriving at the light detector 52. For example, thefirst and second mirror surfaces 67 and 65, respectively, are formed bydepositing a layer of gold atoms onto the inner surface of the outerelectrode 53. Optionally, the first mirror surface 67 directs theinfrared light to the second optical port 57 for detection at detector52. Advantageously, using at least a mirror to redirect the infraredbeam increases the effective path length of the infrared light throughthe sample, thereby providing improved signal to noise when used withdilute samples. Optionally, the infrared source 50 and the detector 52are arranged relative to each other and relative to the outer electrode53 such that infrared light from the source 50 travels through the firstoptical port 55, passes through the 3-dimensional region of spaceproximate the curved surface terminus 33, propagates through the secondoptical port 57, and is detected at detector 52.

[0065] Referring now to FIG. 4, shown is a side cross-sectional view ofthe FAIMS device according to the first embodiment of the instantinvention in a tandem arrangement with a mass spectrometer 60. Elementslabeled with the same numerals have the same function as thoseillustrated in FIG. 2a. The ability to confine ions near the sphericalterminus 33 of the inner FAIMS electrode 32 supports the use ofcomplementary methods of detection. Ions that are selectivelytransmitted and trapped by the applied DV and CV can be probed usinginfrared light, as described with reference to FIG. 2a. Since theinfrared analysis does not consume the ions, these same ions can beextracted into a mass spectrometer 60 for further analysis. Inparticular, an orifice plate 56 of the mass spectrometer 60 ispositioned adjacent to the ion outlet orifice 42 in the outer FAIMSelectrode 44. Ions that exit from the FAIMS analyzer region 40 throughthe ion outlet orifice 42 enter the mass spectrometer 60 after passingthrough an orifice 62 in the orifice plate 56, travel to a skimmer cone58 within the differentially pumped region of the mass spectrometer, andare mass analyzed within a mass analyzer 62.

[0066] In principle, the infrared radiation can also be used to modifythe ions while they are trapped in the 3-dimensional region of spaceproximate the spherical terminus 33 of the inner FAIMS electrode 32. Forexample, the infrared radiation can be used to change the conformationof protein ions or to dissociate loosely held clusters or complexes.Provided that the newly formed “daughter” ions have a stable trajectoryunder the ambient CV and DV conditions, it is then possible to detectthe daughter ions using one of optical and mass spectrometric methods.

[0067] Referring now to FIG. 5, shown is a side cross-sectional view ofthe FAIMS device 30 according to the first embodiment of the instantinvention coupled to a second FAIMS device 70 and to a mass spectrometer60. Elements labeled with the same numerals have the same function asthose illustrated in FIG. 2a. Ions confined within the 3-dimensionalregion of space proximate the spherical terminus 33 of the inner FAIMSelectrode 32 are probed using infrared radiation launched from source 50through the first optical port 48 and received at detector 52 afterpassing through second optical port 49. For example, the infrared lightsource 50 produces infrared light and directs a beam of the producedinfrared light along an optical path including the first optical port48. The confined ions are then extracted through the orifice 42 and intothe second FAIMS 70 through inlet 76. The second FAIMS 70 is aside-to-side FAIMS device, however any other FAIMS electrode geometrycould be used to advantage. The ions are selectively transported througha second analyzer region 80 between an inner FAIMS electrode 74 and anouter FAIMS electrode 72. A high voltage asymmetric waveform and a lowvoltage dc compensation voltage are applied by a second power supply(not shown), to the inner FAIMS electrode 74. Those ions that havestable trajectories under the ambient conditions of CV and DV within thesecond FAIMS are passed through the outlet orifice 78 to the massspectrometer 60. Advantageously, a second different separation of theions can be achieved in order to eliminate some ions that wereco-transported through the first FAIMS 30. The second differentseparation is controlled by varying at least one of the applied DV, theapplied CV, the carrier gas rate, the carrier gas composition, etc.Further advantageously, the identity of the ions that are transmitted bythe first FAIMS 30 can be confirmed using infrared techniques before theions are transported into the second FAIMS 70. This allows a user totune the first FAIMS 30 or the second FAIMS 70 to achieve a desiredresult.

[0068] Referring now to FIG. 6a, shown is a side cross-sectional view ofa FAIMS device 90 according to a second embodiment of the instantinvention. The FAIMS device 90, in the form of a domed-FAIMS device,includes inner and outer cylindrical electrodes 92 and 104,respectively, which are supported by an electrically insulating material98 in an overlapping, spaced-apart arrangement. The generally annularspace between the inner electrode 92 and the outer electrode 104 definesa FAIMS analyzer region 100. The width of the analyzer region 100 isapproximately uniform around the circumference of the inner electrode92, and extends around a curved surface terminus 93 of the innerelectrode 92. An ion inlet orifice 95 is provided through the outerelectrode 104 for introducing ions from an ion source 108 into theanalyzer region 100. A flow of a carrier gas, which is represented inthe figure by a series of closed-headed arrows, is provided within theanalyzer region 100 to carry the ions toward an ion outlet orifice 102located opposite the curved surface terminus 93 of the inner electrode92. An orifice 99 within a curtain plate electrode 127 allows for theflow of a portion of the carrier gas in a direction that iscounter-current to the direction in which the ions are traveling nearthe ion inlet 95, so as to desolvate the ions before they are introducedinto the analyzer region 100. The inner electrode 92 is provided with anelectrical contact 96 through the insulating material 98 for connectionto a power supply 94 that during use is capable of applying a highvoltage asymmetric waveform voltage (DV) and a low voltage dccompensation voltage (CV) to the inner FAIMS electrode 92.

[0069] During use, ions are produced at the ion source 108 from asuitable sample containing a species of interest. Typically, a mixtureincluding a plurality of different ion types is produced when the sampleis ionized. A potential gradient is used in order to accelerate the ionsof the mixture away from the ion source 108, through the orifice 99 inthe curtain plate electrode 97, and toward the ion inlet orifice 95,where the ions become entrained in the carrier gas flow and are carriedinto the FAIMS analyzer region 100. Once inside the FAIMS analyzerregion 100, the ions are carried through an electric field that isformed within the FAIMS analyzer region 100 by the application of the DVand the CV to the inner FAIMS electrode 92 via the electrical contact96. Ion separation occurs within the FAIMS analyzer region 100 on thebasis of the high field mobility properties of the ions. Those ions ofthe mixture that have a stable trajectory for a particular combinationof DV and CV are selectively transmitted through the FAIMS analyzerregion 100, whilst other ions of the mixture collide with an electrodesurface and are lost. Since the electric field also extends around thecurved surface terminus 93, the selectively transmitted ions tend to bedirected generally radially inwardly towards the ion outlet orifice 102.Near trapping conditions are created within the analyzer region 100 byadjusting at least one of the carrier gas flow rate, the carrier gascomposition, the applied CV, the applied DV, the distance between thecurved surface terminus 93 and the ion outlet orifice 102, thetemperature of the carrier gas and the pressure of the carrier gas.Under trapping conditions, which are created within the analyzer region100 by adjusting at least one of the above-mentioned parameters to adifferent value, the selectively transmitted ions accumulate within a3-dimensional region of space proximate the curved surface terminus 93.Under near-trapping conditions the ions also accumulate within the3-dimensional region of space proximate the curved surface terminus 93,except that a lower ion density is achieved when operating undernear-trapping conditions, since the ions are being continually extractedfrom the 3-dimensional region of space as an approximately collimatedbeam of ions. The extracted ions are carried by the carrier gas flowthrough the ion outlet orifice 102.

[0070] According to the second embodiment of the instant invention, thedetection of ions confined in the trapping region of a FAIMS device isperformed using a light scattering technique. Raman spectroscopy is anon-limiting example of a light scattering technique suitable for usewith the second embodiment of the instant invention. If, during acollision between a photon and an ion in the gas phase, the energy ofthe photon corresponds to an energy difference between the state thatthe ion is in and a higher state, the photon may be absorbed. However,no matter what the energy of the photon is, the photon-ion collision mayscatter the photon, thereby changing the photon's direction of motion.Most of the scattered photons undergo no change in frequency and energy.A small fraction however, exchange energy with the ion during thecollision process. The resulting increase or decrease in energy of thescattered photons is the Raman effect.

[0071] Referring still to FIG. 6a, a light source 110 is provided forlaunching substantially monochromatic light, shown schematically with adashed line ending with an open-headed arrow, through a first opticalport 112 in the outer FAIMS electrode 104. For example, the light source110 produces substantially monochromatic light and directs a beam of theproduced substantially monochromatic along an optical path including thefirst optical port 112. Preferably, the light source 110 is in the formof a laser light source for providing laser light of any convenientfrequency v_(o), where v_(o) usually lies in the visible or near-UVregion. Preferably, the first optical port 112 is disposed along thelength of the outer electrode 104 at a point that is substantiallyaligned with the 3-dimensional region of space proximate the sphericalterminus 93. Accordingly, the light from light source 110 is directedthrough a region of higher ion density within the 3-dimensional regionof space. A second optical port 114 is disposed within the outer FAIMSelectrode 104 at a point that is approximately opposite the firstoptical port 112. Light that is not scattered by ions within the3-dimensional region of space proximate the spherical terminus 93 istransmitted out of the FAIMS device 90 through the second optical port114. Optionally, a beam stop is provided in optical communication withthe second optical port 114.

[0072] Referring now to FIG. 6b, shown is a simplified end-on view ofthe FAIMS device of FIG. 6a. Elements labeled with the same numeralshave the same function as those illustrated in FIG. 6a. A detector 118is provided in optical communication with a third optical port 117 forreceiving the light, shown as a wavy dotted line, that is scattered fromthe ions confined within the 3-dimensional region of space proximate thecurved terminus 93 of the inner FAIMS electrode 92. The third opticalport 117 is constructed to be substantially transmissive to thescattered light. Preferably, the third optical port 117 is disposed suchthat the incident laser light is substantially precluded from impingingupon the detector 118 whilst the scattered light is being observed. Thedetector 118 provides an electrical signal relating to an intensity ofthe scattered light. Of course, the first optical port 112 and the thirdoptical port 117 are preferably of a size that is sufficiently large tosupport the propagation of the incident laser light and the scatteredlight, respectively, therethrough. Furthermore, the first optical port1112, the second optical port 114 and the third optical port 117 arepreferably of a size that is sufficiently small such that the electricfields within the analyzer region are substantially unaffected by thediscontinuity in the electrode material. Optionally, one of the opticalport configurations described with reference to FIGS. 2c to 2 f may beused with the FAIMS device 90 according to the second embodiment ofinstant invention.

[0073] During use, trapping conditions are maintained within theanalyzer region 100 as described above, such that the selectivelytransmitted ions accumulate within the 3-dimensional region of spaceadjacent to the spherical terminus 93 of the inner electrode 92. Thisregion of space becomes enriched with ions relative to other regions ofspace within the analyzer region. The incident laser light is passedthrough the 3-dimensional region of space, where the accumulated ionsmay scatter some of the laser light. Of course, the scattering crosssection of ions is very small, hence a sufficiently high ion density andan intense laser beam are necessary in order to achieve an amount ofscattering that can be detected at detector 118.

[0074] Optionally, the analyzer is operated in the near-trapping mode soas to continually extract ions from the 3-dimensional region of space.For example, the extracted ions are provided to one of a second FAIMSdevice and a mass spectrometer for additional separation and detection.Further optionally, the analyzer is operated in a pulsed trapping modeso as to provide packets of ions at intervals of time for one ofadditional separation and detection.

[0075] Referring now to FIG. 7a, shown is a side cross-sectional view ofanother FAIMS device 120 according to the second embodiment of theinstant invention. The FAIMS device 120, in the form of a domed-FAIMSdevice, includes inner and outer cylindrical electrodes 122 and 136,respectively, which are supported by an electrically insulating material128 in an overlapping, spaced-apart arrangement. The generally annularspace between the inner electrode 122 and the outer electrode 136defines a FAIMS analyzer region 132. The width of the analyzer region132 is approximately uniform around the circumference of the innerelectrode 122, and extends around a curved surface terminus 123 of theinner electrode 122. An ion inlet orifice 130 is provided through theouter electrode 136 for introducing ions from an ion source 140 into theanalyzer region 132. A flow of a carrier gas, which is represented inthe figure by a series of closed-headed arrows, is provided within theanalyzer region 132 to carry the ions toward an ion outlet orifice 134located opposite the curved surface terminus 123 of the inner electrode122. An orifice 129 within a curtain plate electrode 127 allows for theflow of a portion of the carrier gas in a direction that iscounter-current to the direction in which the ions are traveling nearthe ion inlet 130, so as to desolvate the ions before they areintroduced into the analyzer region 132. The inner electrode 122 isprovided with an electrical contact 126 through the insulating material128 for connection to a power supply 124 that during use is capable ofapplying a high voltage asymmetric waveform voltage (DV) and a lowvoltage dc compensation voltage (CV) to the inner FAIMS electrode 122.

[0076] During use, ions are produced at the ion source 140 from asuitable sample containing a species of interest. Typically, a mixtureincluding a plurality of different ion types is produced when the sampleis ionized. A potential gradient is used in order to accelerate the ionsof the mixture away from the ion source 140, through the orifice 129 inthe curtain plate electrode 127, and toward the ion inlet orifice 130,where the ions become entrained in the carrier gas flow and are carriedinto the FAIMS analyzer region 132. Once inside the FAIMS analyzerregion 132, the ions are carried through an electric field that isformed within the FAIMS analyzer region 132 by the application of the DVand the CV to the inner FAIMS electrode 122 via the electrical contact126. Ion separation occurs within the FAIMS analyzer region 132 on thebasis of the high field mobility properties of the ions. Those ions ofthe mixture that have a stable trajectory for a particular combinationof DV and CV are selectively transmitted through the FAIMS analyzerregion 132, whilst other ions of the mixture collide with an electrodesurface and are lost. Since the electric field also extends around thecurved surface terminus 123, the selectively transmitted ions tend to bedirected generally radially inwardly towards the ion outlet orifice 134.Near trapping conditions are created within the analyzer region 132 byadjusting at least one of the carrier gas flow rate, the carrier gascomposition, the applied CV, the applied DV, the distance between thecurved surface terminus 123 and the ion outlet orifice 134, thetemperature of the carrier gas and the pressure of the carrier gas.Under trapping conditions, which are created within the analyzer region132 by adjusting at least one of the above-mentioned parameters to adifferent value, the selectively transmitted ions accumulate within a3-dimensional region of space proximate the curved surface terminus 123.Under near-trapping conditions the ions also accumulate within the3-dimensional region of space proximate the curved surface terminus 123,except that a lower ion density is achieved when operating undernear-trapping conditions, since the ions are being continually extractedfrom the 3-dimensional region of space as an approximately collimatedbeam of ions. The extracted ions are carried by the carrier gas flowthrough the ion outlet orifice 134.

[0077] Referring still to FIG. 7a, the FAIMS inner electrode 122 has achannel 142 extending therethrough. A first optical port 144 is disposedwithin the channel 42, proximate the curved surface terminus 123. Alight source 146 is provided for launching substantially monochromaticlight, shown schematically with a dashed line ending with an open arrow,into the channel 142 and through the first optical port 144 in the innerFAIMS electrode 122. For example, the light source 146 producessubstantially monochromatic light and directs a beam of the producedsubstantially monochromatic light along an optical path including thefirst optical port 144. Preferably, the light source 146 is in the formof a laser light source for providing laser light of any convenientfrequency v_(o), where v_(o) usually lies in the visible or near-UVregion. Ions that are confined in the trapping region scatter a portionof the incident radiation with a portion thereof going to a detector 148after passing through a second optical port 150 in the outer FAIMSelectrode 136. Light that is not scattered by ions within the3-dimensional region of space proximate the spherical terminus 123 istransmitted out of the FAIMS device 120 through the ion outlet orifice134. Optionally, a beam stop is provided in optical communication withthe ion outlet orifice 134. Of course, the first optical port 144 andthe second optical port 150 are preferably of a size that issufficiently large to support the propagation of the incident laserlight and the scattered light, respectively, therethrough. Furthermore,the first optical port 144 and the second optical port 150 arepreferably of a size that is sufficiently small such that the electricfields within the analyzer region are substantially unaffected by thediscontinuity in the electrode material. Optionally, one of the opticalport configurations described with reference to FIGS. 2c to 2 f may beused with the FAIMS device 120 according to the second embodiment ofinstant invention.

[0078] Referring now to FIG. 7b, shown is a simplified end-on view ofthe FAIMS device of FIG. 7a. Elements labeled with the same numeralshave the same function as those illustrated in FIG. 7a. The black dot inFIG. 7b indicates from this view that the laser radiation is coming outof the page toward the reader. In this case, the scattered light isobserved at right angles to the incident laser light. Of course, thescattered light may be observed at any appropriate angle. The detector148 provides an electrical signal relating to an intensity of thescattered light.

[0079] In addition to the incident light being scattered by interactionswith the ions confined within the FAIMS analyzer, light scattering alsooccurs if the ions heat a small volume of the surrounding bath gas. Thephotons of the incident light scatter as they pass into a hot gasbecause such a heated “bubble” of gas has a different refractive indexthan the cooler surrounding gas. One way of inducing the ions to heat asmall volume of the surrounding bath gas is to adjust the asymmetricwaveform that is applied to the inner electrode of a FAIMS device. Sincethe application of the asymmetric waveform results in the ionsoscillating back and forth in approximately a same region of space, thegas that surrounds an ion becomes heated around the trajectory of theion. This oscillation requires energy, and this energy is dissipated tocreate a region in the vicinity of the ion where the gas is hotter thanthe bulk of the gas in the FAIMS device. This region of heated gas issignificantly larger in size than the ion, and is more likely to scatterthe light than the relatively small ion itself. Of course, theoscillation of any ion present in the trapping region gives rise toheating of the bath gas. In other words, the ions that are detected maynot be the ion of interest, despite the fact that they are transmittedat the same CV value. Accordingly, there may not be as much specificityas there would be in looking at the scattered light from the ion itself,as described above. Tandem FAIMS devices may be more appealing forstudying gas phase ions based on the heating of the bath gas because ofthe extra specificity as opposed to a single FAIMS device.Alternatively, the non-destructive nature of the detection methodsupports the combination of light scattering detection methods with massspectrometry in order to achieve more specificity if desired.

[0080] The FAIMS device 90 that was described with reference to FIGS. 6aand 6 b, as well as the FAIMS device 120 that was described withreference to FIGS. 7a and 7 b, is suitable for detecting ions based uponthe scattering of incident light as a result of bath gas heating by theions. Application of a high voltage, high frequency asymmetric waveformto the ions in the analyzer region of FAIMS causes the ions to moverapidly back and forth through the gas in an oscillatory motion. Theenergy provided to the ions to cause this motion is dissipated,effectively by the equivalent of friction, to the gas and causes heatingof the gas in the vicinity of the ion. This heated gaseous regionbecomes a lens of different refractive index than the bulk gas, and canscatter incident light. If the ion is being carried along the analyzerregion of FAIMS, the ion and the heated region remain, together as theymove in concert along the length of the analyzer. The heat produced bythe ion therefore continues to heat the same volume of gas, whosetemperature continues to rise. On the other hand, if the ion enters atrapping or near trapping region of FAIMS this condition changes. Theion is constrained by the focusing effects of the electric fields, andthe gas flows past the ion. In this case the heat generated by theoscillating ion is applied to continuously new volumes of gas that flowpast the ion, and the heat is carried away by the flow of gas.

[0081] For example, in FIG. 7a, an ion A is flowing along with the gasas described in the first case in the previous paragraph. This maximizesthe temperature of the gas in the vicinity of ion A. On the other handan ion B, which is located within the 3-dimensional region of spaceproximate the curved surface terminus 123 of the inner electrode 122,feels the contrary forces of the electric fields and gas flows, and someof the heat produced by the ion B is carried away by the gas out of theorifice 134.

[0082] Referring now to FIG. 8, shown is a side cross-sectional view ofa FAIMS device 160 according to a third embodiment of the instantinvention. The FAIMS device 160, in the form of a domed-FAIMS device,includes inner and outer cylindrical electrodes 162 and 176,respectively, which are supported by an electrically insulating material168 in an overlapping, spaced-apart arrangement. The generally annularspace between the inner electrode 162 and the outer electrode 176defines a FAIMS analyzer region 172. The width of the analyzer region172 is approximately uniform around the circumference of the innerelectrode 162, and extends around a curved surface terminus 163 of theinner electrode 162. An ion inlet orifice 170 is provided through theouter electrode 176 for introducing ions from an ion source 180 into theanalyzer region 172. A flow of a carrier gas, which is represented inthe figure by a series of closed-headed arrows, is provided within theanalyzer region 172 to carry the ions toward an ion outlet orifice 174located opposite the curved surface terminus 163 of the inner electrode162. An orifice 169 within a curtain plate electrode 167 allows for theflow of a portion of the carrier gas in a direction that iscounter-current to the direction in which the ions are traveling nearthe ion inlet 170, so as to desolvate the ions before they areintroduced into the analyzer region 172. The inner electrode 162 isprovided with an electrical contact 166 through the insulating material168 for connection to a power supply 164 that during use is capable ofapplying a high voltage asymmetric waveform voltage (DV) and a lowvoltage de compensation voltage (CV) to the inner FAIMS electrode 162.

[0083] During use, ions are produced at the ion source 180 from asuitable sample containing a species of interest. Typically, a mixtureincluding a plurality of different ion types is produced when the sampleis ionized. A potential gradient is used in order to accelerate the ionsof the mixture away from the ion source 180, through the orifice 169 inthe curtain plate electrode 167, and toward the ion inlet orifice 170,where the ions become entrained in the carrier gas flow and are carriedinto the FAIMS analyzer region 172. Once inside the FAIMS analyzerregion 172, the ions are carried through an electric field that isformed within the FAIMS analyzer region 172 by the application of the DVand the CV to the inner FAIMS electrode 162 via the electrical contact166. Ion separation occurs within the FAIMS analyzer region 172 on thebasis of the high field mobility properties of the ions. Those ions ofthe mixture that have a stable trajectory for a particular combinationof DV and CV are selectively transmitted through the FAIMS analyzerregion 172, whilst other ions of the mixture collide with an electrodesurface and are lost. Since the electric field also extends around thecurved surface terminus 163, the selectively transmitted ions tend to bedirected generally radially inwardly towards the ion outlet orifice 174.Near trapping conditions are created within the analyzer region 172 byadjusting at least one of the carrier gas flow rate, the carrier gascomposition, the applied CV, the applied DV, the distance between thecurved surface terminus 163 and the ion outlet orifice 174, thetemperature of the carrier gas and the pressure of the carrier gas.Under trapping conditions, which are created within the analyzer region173 by adjusting at least one of the above-mentioned parameters to adifferent value, the selectively transmitted ions accumulate within a3-dimensional region of space proximate the curved surface terminus 163.Under near-trapping conditions the ions also accumulate within the3-dimensional region of space proximate the curved surface terminus 163,except that a lower ion density is achieved when operating undernear-trapping conditions, since the ions are being continually extractedfrom the 3-dimensional region of space as an approximately collimatedbeam of ions. The extracted ions are carried by the carrier gas flowthrough the ion outlet orifice 174.

[0084] The applied high voltage asymmetric waveform causes an ion withinthe analyzer region 173 to experience a rapid oscillatory motion thatleads to energetic collisions with the surrounding bath gas. Thesecollisions result in “heating” of an ion as it moves through the bathgas, as was described in more detail above. Ions that are heated by thehigh electric fields in the FAIMS device may also emit some of theirenergy. For example, molecules that absorb infrared radiation are alsocapable of emitting characteristic infrared wavelengths when heated forexample by collisions with the bath gas molecules. This emittedradiation can be monitored to probe the ions confined in the trappingregion of the FAIMS device. Accordingly, the power supply 164 is anotherexample of a probe signal generator.

[0085] Referring still to FIG. 8, the FAIMS device 160 includes anoptical port 182 in the outer FAIMS electrode 176. The optical port 182supports the propagation of infrared light, including infrared lighthaving a wavelength within a wavelength range of interest, therethrough.Preferably, the optical port 182 is disposed along the length of theouter electrode 176 at a point that is substantially aligned with the3-dimensional region of space proximate the spherical terminus 163.Accordingly, the infrared light emitted by the ions that are confinedwithin the 3-dimensional region of space passes through the optical port182 to a light detector 184. The detector 184 is in opticalcommunication with the optical port 182 for receiving the emittedinfrared light propagating therethrough, and for providing an electricalsignal relating to an intensity of the emitted infrared light having awavelength within the wavelength range of interest. Of course, theoptical port 182 is of a size that is sufficiently large to transmit theemitted infrared light. Furthermore, the optical port 182 issufficiently small such that the electric fields within the analyzerregion 172 are substantially unaffected by the discontinuity in theelectrode material. Optionally, one of the optical port configurationsdescribed with reference to FIGS. 2c to 2 f may be used with the FAIMSdevice 160 according to the third embodiment of instant invention.

[0086] Referring still to FIG. 8, the detector 184 is preferably placedproximate the trapping region. Having the detector 184 in the regionnear the gas outlet 174 reduces the effect of the emission of ions otherthan the ions of interest compared with having the detector in theregion near the ion inlet 170. In addition, the ion density in thetrapping region proximate the spherical terminus 163 of the inner FAIMSelectrode 162 can be significantly higher than the ion density in theanalyzer region when the operating parameters are selected to optimizeion trapping. The higher ion density results in more radiation beingemitted from the trapping region and therefore a more intense signal isacquired. The amount of heating required by the application of theasymmetric waveform to trigger characteristic emission events in an ionmay be variable. Consequently, emission spectra may be acquired as afunction of the DV to give multiple fingerprint spectra that arespecific for a given analyte, as a function of DV, since the emission isspecific to the structure of the species. As was described above, acommon method for determining the identity of an unknown compound usingIR detection involves comparing the unknown sample with a library ofknown compounds and reporting the most likely matches. For this example,however, the emission spectra may change as a function of the appliedwaveform voltage. Thus, reference spectra at different applied waveformvoltages should be used for comparative purposes.

[0087] Optionally, the analyzer is operated in the near-trapping mode soas to continually extract ions from the 3-dimensional region of space.For example, the extracted ions are provided to one of a second FAIMSdevice and a mass spectrometer for additional separation and detection.Further optionally, the analyzer is operated in a pulsed trapping modeso as to provide packets of ions at intervals of time for one ofadditional separation and detection.

[0088] Referring now to FIG. 9, shown is a side cross-sectional view ofanother FAIMS device according to the third embodiment of the instantinvention. Elements labeled with the same numerals have the samefunction as those illustrated in FIG. 8. The FAIMS device 190, in theform of a domed-FAIMS device, includes an outer FAIMS electrode 192having an optical port 194 that is disposed along a length thereof at apoint that is intermediate the ion inlet 170 and the curved surfaceterminus 163. Of course, heating of the ions occurs throughout the FAIMSdevice 190 when the asymmetric waveform is operated at high voltage.Thus, the FAIMS device 190 does not require a light source in order toexcite the ions within the analyzer region 172, which simplifies theset-up and reduces the cost to produce the apparatus. In addition, theheating of the ions is not restricted to the ions that are confined inthe trapping region, but instead ions throughout the FAIMS deviceexperience heating. Thus, the placement of the detector is not asrestricted as it is in the first and second embodiments of the instantinvention. For the FAIMS device 190, the optical port 194 in the outerFAIMS electrode 192 may be disposed at one of a plurality of locationsalong the outer FAIMS electrode 176 in the region between the ion inletand ion outlet. Of course, locating the optical port 194 too close tothe ion inlet 170, however, may result in a condition in which there isa greater contribution to the background because of emission from ionsother than the ion of interest. This occurs if ions other than the ionsof interest have not had sufficient time to be lost to the walls of theFAIMS device 190. That is, ions other than the ion of interest, whichtransmit at CV values other than the optimal CV value of the ion ofinterest, require a finite time after they enter the ion inlet beforethey collide with an electrode wall. This time is dependent upon severalparameters that include, but are not limited to, the voltage andfrequency of the asymmetric waveform, the CV of the ion in comparisonwith the ion of interest, etc.

[0089] For improved detection specificity, the invention described withreference to FIG. 8 or 9 is optionally combined with mass spectrometrybased detection. The nondestructive method of measuring the radiationemitted from the ion of interest enables the ion to be further studiedusing mass spectrometry based techniques.

[0090] Optionally, the FAIMS device shown in FIG. 9 is constructed usingother than cylindrical electrode geometry. For instance, a trappingregion is not required, and therefore FAIMS devices having, forinstance, one of parallel plate electrodes, curved plate electrodes andspherical electrodes are suitable. Furthermore, the so-calledside-to-side FAIMS devices could also be used to advantage with theinvention as it is described with reference to FIG. 9.

[0091] In addition to detecting selectively transmitted ions, theabove-mentioned devices are also suitable for affecting a property ofthe selectively transmitted ions. In principle, the IR light can be usedto modify the ions, for example change the conformation of protein ions,or dissociate loosely held clusters or complexes, while the precursorsare trapped in the FAIMS device. The newly formed “daughter” ions thatare formed from these precursor ions can be detected by optical or massspectrometric methods. Similarly, bath gas heating resulting from theapplication of strong electric fields within the FAIMS analyzer regionprovides the energy that is required to affect the conformation ordissociate clusters within the selectively transmitted ions. Of course,changing the structure of a selectively transmitted ion affects its highfield ion mobility properties. As such, a parent ion that has a stabletrajectory under a particular combination of applied DV and CV may forma daughter ion that is lost due to a collision with an electrode underidentical DV and CV conditions.

[0092] Referring now to FIG. 10, shown is a simplified flow diagram fora method of detecting selectively transmitted ions using an opticalbased detection technique. At step 300, a mixture of ions including anion type of interest is introduced into a FAIMS analyzer region of, forexample, one of the above-mentioned FAIMS devices 30, 61, 90, 120, 160and 190. Optionally, the ions are produced within the analyzer regionfrom a suitable sample using, for example, a laser-based ionizationtechnique. At step 302, appropriate conditions are provided within theFAIMS analyzer region for effecting a separation of the ions, toselectively transmit the ion type of interest to a detection portion ofthe analyzer region. For optical based detection techniques involvingone of an absorption and a scattering of incident radiation by theselectively transmitted ions, it is most preferable to confine theselectively transmitted ions within a 3-dimensional region of spaceoverlapping with the detection portion. Confining the selectivelytransmitted ions within the 3-dimensional region of space results in ahigher ion density within the detection portion of the analyzer region,which produces a better response from the light detector. For opticalbased detection techniques involving bath gas heating, it is preferableto probe the ions in a portion of the analyzer region other than the3-dimensional region of space proximate the curved surface terminus ofthe inner electrode. Once ions are being selectively transmitted throughthe analyzer region to the detection portion, a stimulus is provided atstep 304 to the selectively transmitted ions. For example, providing thestimulus includes one of directing an incident beam of infrared lightthrough the detection portion, directing an incident beam of laser lightthrough the detection portion, and applying a strong electric fieldwithin the detection portion. Optionally, a combination including two ormore of the above-mentioned stimuli is provided. The stimulus isprovided such that light including information relating to theselectively transmitted ions results from an interaction between thestimulus and the selectively transmitted ions. The light includinginformation relating to the selectively transmitted ions depends uponthe nature of the stimulus, and includes transmitted infrared light,light that is scattered by one of the selectively transmitted ions andthe carrier gas in the vicinity of a selectively transmitted ion, andinfrared light emitted by the selectively transmitted ions as a resultof bath gas heating of the ions under the influence of strong electricfields within the analyzer region. At step 306 the light includinginformation relating to the selectively transmitted ions is received ata light detector. Preferably, the light is propagated through an opticalport to a detector that is disposed external to the FAIMS analyzerregion. At step 308, at least an intensity of the light includinginformation relating to the selectively transmitted ions is determined.In this case, the information provides a measure of the ionconcentration or of the ion density within the detection portion of theanalyzer region. Preferably, the intensity determination is performed asa function of wavelength, in which case the information also relates toa structural identification of the selectively transmitted ions.Optionally, the selectively transmitted ions are provided to a differentanalyzer or to a mass spectrometer after optical based detection.

[0093] Referring now to FIG. 11, shown is a simplified flow diagram foranother method of detecting selectively transmitted ions using anoptical based detection technique. At step 310, a mixture of ionsincluding an ion type of interest is introduced into a FAIMS analyzerregion of, for example, one of the above-mentioned FAIMS devices 30, 61,90 and 120. Optionally, the ions are produced within the analyzer regionfrom a suitable sample using, for example, a laser-based ionizationtechnique. At step 312, appropriate conditions are provided within theFAIMS analyzer region for effecting a separation of the ions, toselectively transmit the ion type of interest to a detection portion ofthe analyzer region. At step 314, some of the selectively transmittedions are confined within a 3-dimensional region of space overlappingwith the detection portion. Confining the selectively transmitted ionswithin the 3-dimensional region of space results in a higher ion densitywithin the detection portion of the analyzer region, which produces abetter response from the light detector. At step 316, incident light isdirected through the 3-dimensional region of space within the analyzerregion. For example, light from one of an infrared light source and alaser light source is directed through a first light transmissiveoptical port in a direction toward the 3-dimensional region of space. Atstep 318 the incident light is allowed to interact with the selectivelytransmitted ions confined within the 3-dimensional region of space, toresult in light including information relating to the selectivelytransmitted ions. At step 320, the light including information relatingto the selectively transmitted ions is detected. For example, the lightpropagates from the 3-dimensional region of space to a light detectorvia a second light transmissive optical port. Optionally, the light isdetected after propagating through one of the first light transmissiveoptical port and the ion outlet orifice from the FAIMS analyzer region.

[0094] Referring now to FIG. 12, shown is a simplified flow diagram fora method of affecting the selectively transmitted ions. At step 322, amixture of ions including an ion type of interest is introduced into aFAIMS analyzer region of, for example, one of the above-mentioned FAIMSdevices 30, 61, 90, 120, 160 and 190. Optionally, the ions are producedwithin the analyzer region from a suitable sample using, for example, alaser-based ionization technique. At step 324, appropriate conditionsare provided within the FAIMS analyzer region for effecting a separationof the ions, to selectively transmit the ion type of interest to atleast a portion of the analyzer region. At step 326, the ions areaffected in order to induce a change therein. For example, a stimulus isprovided to the selectively transmitted ions at step 326. Somenon-limiting examples of suitable forms of stimuli include: directing anincident beam of infrared light through the at least a portion;directing an incident beam of laser light through the at least aportion; and, applying a strong electric field within the at least aportion. Optionally, a combination including two or more of theabove-mentioned stimuli is provided. Changes that are induced by thestimulus include but are not limited to: conformational changes;dissociation of weakly bound molecules; and, chemical bond breakage.Ions formed when the selectively transmitted ions undergo such a changeare referred to herein as “daughter ions”. At step 328 the daughter ionsare detected. Of course, daughter ions may only be detected if they havehigh field mobility properties that are suitable for transmitting thedaughter ions within the FAIMS analyzer region under the ambientconditions of applied CV, applied DV, carrier gas flow rate, etc.Optionally, the daughter ions are detected using one of an optical baseddetection technique, a mass spectrometric detection technique andelectrometric detection.

[0095] Referring now to FIG. 13, shown is a simplified flow diagram foranother method of affecting the selectively transmitted ions. At step330, a mixture of ions including an ion type of interest is introducedinto a FAIMS analyzer region of, for example, one of the above-mentionedFAIMS devices 30, 61, 90 and 120. Optionally, the ions are producedwithin the analyzer region from a suitable sample using, for example, alaser-based ionization technique. At step 332, appropriate conditionsare provided within the FAIMS analyzer region for effecting a separationof the ions, to selectively transmit the ion type of interest to areaction portion within the analyzer region. At step 334, some of theselectively transmitted ions are confined within a 3-dimensional regionof space overlapping with the reaction portion. Confining theselectively transmitted ions within the 3-dimensional region of spaceresults in a higher ion density within the reaction portion of theanalyzer region. At step 336, incident light is directed through the3-dimensional region of space within the analyzer region. For example,light from one of an infrared light source and a laser light source isdirected through a first light transmissive optical port in a directiontoward the 3-dimensional region of space. At least one of the intensityand the frequency of the incident light is selected to affect the ionswithin the 3-dimensional region of space. At step 338 the incident lightis allowed to interact with the selectively transmitted ions confinedwithin the 3-dimensional region of space, to produce daughter ions. Thedaughter ions are formed from the selectively transmitted ions as aresult of structural changes that include but are not limited to:conformational changes; dissociation of weakly bound molecules; and,chemical bond breakage. The daughter ions are detected at step 340. Ofcourse, daughter ions may only be detected if they have high fieldmobility properties that are suitable for transmitting the daughter ionswithin the FAIMS analyzer region under the ambient conditions of appliedCV, applied DV, carrier gas flow rate, etc. Optionally, the daughterions are detected using one of an optical based detection technique, amass spectrometric detection technique and electrometric detection.

[0096] Some non-limiting examples of optional features that may beemployed in conjunction with the various embodiments of the instantinvention will now be described briefly. The light transmissive windowmaterial that is used to form an optical port is optionally one of alight focusing element and a light dispersing element. Furtheroptionally, a reflective surface is provided within the FAIMS analyzerregion for directing light that propagates from a light source though anoptical port back through the optical port to a detector element.Advantageously, the path length of the light through the gaseous sampleis increased and only a single optical port is required.

[0097] Numerous other embodiments may be envisaged without departingfrom the spirit and scope of the invention.

What is claimed is:
 1. An apparatus for separating ions in the gasphase, comprising: a high field asymmetric waveform ion mobilityspectrometer comprising two electrodes defining an analyzer regiontherebetween, the two electrodes disposed in a spaced apart arrangementfor allowing ions to propagate therebetween and for providing anelectric field within the analyzer region resulting from the applicationof an asymmetric waveform voltage to at least one of the two electrodesand from the application of a compensation voltage, to at least one ofthe two electrodes, for selectively transmitting a first type of ionalong an average ion flow path within the analyzer region at a givencombination of asymmetric waveform voltage and compensation voltage; anoptical port disposed within a surface of one of the two electrodes andadjacent to an ion detecting portion of the analyzer region, the opticalport for propagating light including information relating to theselectively transmitted ions therethrough; and, a light detectordisposed external to the ion detecting portion of the analyzer regionand in optical communication with the optical port for receiving thelight including information relating to the selectively transmitted ionswithin the ion detecting portion and for providing an electrical signalrelating to at least an intensity of the received light.
 2. An apparatusaccording to claim 1, wherein the optical port is formed of a materialthat is transmissive to light including the light including informationrelating to the selectively transmitted ions.
 3. An apparatus accordingto claim 1, wherein the analyzer region includes an inlet orifice and anoutlet orifice for introducing a gas flow between the two electrodes andthrough the analyzer region.
 4. An apparatus according to claim 3,wherein the optical port is in communication with a gas source fordirecting a supplemental gas flow through the optical port formaintaining the gas flow through the analyzer region in a direction thatis generally along the average ion flow path.
 5. An apparatus accordingto claim 1, wherein the light detector other than consumes the ionsduring ion detection within the ion detecting portion of the analyzerregion.
 6. An apparatus according to claim 5, wherein the light detectoris in the form of an infrared detector for detecting light within theinfrared portion of the electromagnetic spectrum.
 7. An apparatusaccording to claim 1, comprising an ion outlet orifice of the analyzerregion disposed along the average ion flow path for extracting theselectively transmitted ions from the analyzer region subsequent to iondetection within the detecting portion of the analyzer region.
 8. Anapparatus according to claim 7, comprising a mass spectrometer externalto the analyzer region and in communication with the ion outlet orificeof the analyzer region for receiving the selectively transmitted ionsextracted therethrough and for performing a mass-to-charge analysis ofthe extracted ions.
 9. An apparatus according to claim 3, wherein thetwo electrodes comprise first and second electrodes defining a spacetherebetween, the space forming the analyzer region, wherein, in use, atleast one of the asymmetric waveform voltage, the compensation voltageand the gas flow are adjustable, so as to confine some of theselectively transmitted ions within a 3-dimensional region of spacewithin the ion detecting portion of the analyzer region.
 10. Anapparatus according to claim 9, wherein the optical port is disposedwithin a surface of one of the first and second electrodes at a pointthat is approximately aligned with the 3-dimensional region of spacewithin the ion detecting portion of the analyzer region.
 11. Anapparatus for separating ions in the gas phase, comprising: a high fieldasymmetric waveform ion mobility spectrometer comprising two electrodesdefining an analyzer region therebetween, the two electrodes disposed ina spaced apart arrangement for allowing ions to propagate therebetweenand for providing an electric field within the analyzer region resultingfrom the application of an asymmetric waveform voltage to at least oneof the two electrodes and from the application of a compensation voltageto at least one of the two electrodes, for selectively transmitting afirst type of ion along an average ion flow path within the analyzerregion at a given combination of asymmetric waveform voltage andcompensation voltage; and, an optical detector spaced apart from theaverage ion flow path for receiving light including information relatingto the selectively transmitted ions within the average ion flow path soas to support a non-destructive determination of a characteristic of theselectively transmitted ions.
 12. A method for separating ions in thegas phase, comprising the steps of: separating a mixture of ionsincluding ions of a first type by selectively transmitting the ions ofthe first type through an analyzer region of a high field asymmetricwaveform ion mobility spectrometer along an average ion flow pathbetween an ion inlet end of the analyzer region and an ion outlet end ofthe analyzer region; detecting light including information relating tothe selectively transmitted ions using a light detector that is spacedapart from the average ion flow path; and, determining a characteristicof the selectively transmitted ions based on the detected lightincluding information relating to the selectively transmitted ions. 13.A method according to claim 12, including the step, subsequent to thestep of detecting light including information relating to theselectively transmitted ions, of extracting the selectively transmittedions from the analyzer region.
 14. A method according to claim 12,wherein the step of detecting light including information relating tothe selectively transmitted ions is performed at a point along theaverage ion flow path that is intermediate the ion inlet end of theanalyzer region and an ion outlet end of the analyzer region.
 15. Amethod according to claim 14, wherein the step of separating a mixtureof ions includes a step of applying an asymmetric waveform voltageacross the analyzer region, and wherein the asymmetric waveform voltageresults in the emission of the light including information relating tothe selectively transmitted ions.
 16. A method according to claim 12,wherein the step of detecting light including information relating tothe selectively transmitted ions is performed at a point along theaverage ion flow path that is proximate the ion outlet end of theanalyzer region.
 17. A method according to claim 16, including the stepof confining some of the selectively transmitted ions within a3-dimensional region of space at the point along the average ion flowpath that is proximate the ion outlet end of the analyzer region.
 18. Amethod according to claim 17, including the step of directing incidentlight through the selectively transmitted ions within the 3-dimensionalregion of space.
 19. A method according to claim 18, wherein the lightincluding information relating to the selectively transmitted ionscomprises a portion of the incident light that is other than absorbed bythe selectively transmitted ions within the 3-dimensional region ofspace.
 20. A method according to claim 18, wherein the light includinginformation relating to the selectively transmitted ions comprises aportion of the incident light that is scattered as a result of thepassage of the incident light through the 3-dimensional region of space.21. A method according to claim 18, wherein the light includinginformation relating to the selectively transmitted ions comprises lightemitted by the selectively transmitted ions within the 3-dimensionalregion of space.
 22. A method according to claim 12, wherein the lightincluding information relating to the selectively transmitted ionscomprises light having a wavelength within the infrared portion of theelectromagnetic spectrum.